Enantio- and Diastereoselective Michael Reaction of 1,3-Dicarbonyl Compounds to Nitroolefins Catalyzed by a Bifunctional Thiourea

We synthesized a new class of bifunctional catalysts bearing a thiourea moiety and an amino
group on a chiral scaffold. Among them, thiourea 1e bearing 3,5-bis(trifluoromethyl)benzene and
dimethylamino groups was revealed to be highly efficient for the asymmetric Michael reaction of
1,3-dicarbonyl compounds to nitroolefins. Furthermore, we have developed a new synthetic route for
(R)-(−)-baclofen and a chiral quaternary carbon center with high enantioselectivity by Michael reaction. In
these reactions, we assumed that a thiourea moiety and an amino group of the catalyst activates a nitroolefin
and a 1,3-dicarbonyl compound, respectively, to afford the Michael adduct with high enantio- and
diastereoselectivity.